This paper deals with the control of smallpox in the colonial city of Dar es Salaam in Tanzania. Specifically, it investigates city authorities’ control measures and residents’ responses to the measures, and the lessons to be derived for the current initiatives to prevent pandemics such as COVID-19 and Monkeypox. By drawing on secondary, archival, and newspaper sources, the chapter has established that the authorities took various anti-smallpox initiatives including vaccination, patient isolation, public health education, restricting people’s movements, the demand for vaccination certificates for immigrants, and the prosecution of residents. The residents’ responses to the initiatives varied from acquiescence to resistance. The study of the measures and responses lays bare the nature of authorities, economy, racism, blame, and othering, and people’s agency. Moreover, the responses and measures offer us lessons that can be applied for the control of the current COVID-19, Mpox, and other pandemics. The lessons include the need to redress problems that weakened past initiatives to combat epidemics, as well as learning good practices from the past. This chapter adds to the growing body of literature on urban history of diseases that links local diseases and control measures with national, imperial (colonial), and global initiatives.